1me9: Difference between revisions
New page: left|200px<br /><applet load="1me9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1me9, resolution 2.2Å" /> '''Inosine Monophosphate... |
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[[Image:1me9.gif|left|200px]]<br /><applet load="1me9" size=" | [[Image:1me9.gif|left|200px]]<br /><applet load="1me9" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1me9, resolution 2.2Å" /> | caption="1me9, resolution 2.2Å" /> | ||
'''Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP bound'''<br /> | '''Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP bound'''<br /> | ||
==Overview== | ==Overview== | ||
The enzyme inosine monophosphate dehydrogenase (IMPDH) is responsible for | The enzyme inosine monophosphate dehydrogenase (IMPDH) is responsible for the rate-limiting step in guanine nucleotide biosynthesis. Because it is up-regulated in rapidly proliferating cells, human type II IMPDH is actively targeted for immunosuppressive, anticancer, and antiviral chemotherapy. The enzyme employs a random-in ordered-out kinetic mechanism where substrate or cofactor can bind first but product is only released after the cofactor leaves. Due to structural and kinetic differences between mammalian and microbial enzymes, most drugs that are successful in the inhibition of mammalian IMPDH are far less effective against the microbial forms of the enzyme. It is possible that with greater knowledge of the structural mechanism of the microbial enzymes, an effective and selective inhibitor of microbial IMPDH will be developed for use as a drug against multi-drug resistant bacteria and protists. The high-resolution crystal structures of four different complexes of IMPDH from the protozoan parasite Tritrichomonas foetus have been solved: with its substrate IMP, IMP and the inhibitor mycophenolic acid (MPA), the product XMP with MPA, and XMP with the cofactor NAD(+). In addition, a potassium ion has been located at the dimer interface. A structural model for the kinetic mechanism is proposed. | ||
==About this Structure== | ==About this Structure== | ||
1ME9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Tritrichomonas_foetus Tritrichomonas foetus] with K and IMP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/IMP_dehydrogenase IMP dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.205 1.1.1.205] Full crystallographic information is available from [http:// | 1ME9 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Tritrichomonas_foetus Tritrichomonas foetus] with <scene name='pdbligand=K:'>K</scene> and <scene name='pdbligand=IMP:'>IMP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/IMP_dehydrogenase IMP dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.205 1.1.1.205] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ME9 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Tritrichomonas foetus]] | [[Category: Tritrichomonas foetus]] | ||
[[Category: Luecke, H.]] | [[Category: Luecke, H.]] | ||
[[Category: Prosise, G | [[Category: Prosise, G L.]] | ||
[[Category: IMP]] | [[Category: IMP]] | ||
[[Category: K]] | [[Category: K]] | ||
[[Category: alpha beta barrel]] | [[Category: alpha beta barrel]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:22 2008'' | ||
Revision as of 14:54, 21 February 2008
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Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP bound
OverviewOverview
The enzyme inosine monophosphate dehydrogenase (IMPDH) is responsible for the rate-limiting step in guanine nucleotide biosynthesis. Because it is up-regulated in rapidly proliferating cells, human type II IMPDH is actively targeted for immunosuppressive, anticancer, and antiviral chemotherapy. The enzyme employs a random-in ordered-out kinetic mechanism where substrate or cofactor can bind first but product is only released after the cofactor leaves. Due to structural and kinetic differences between mammalian and microbial enzymes, most drugs that are successful in the inhibition of mammalian IMPDH are far less effective against the microbial forms of the enzyme. It is possible that with greater knowledge of the structural mechanism of the microbial enzymes, an effective and selective inhibitor of microbial IMPDH will be developed for use as a drug against multi-drug resistant bacteria and protists. The high-resolution crystal structures of four different complexes of IMPDH from the protozoan parasite Tritrichomonas foetus have been solved: with its substrate IMP, IMP and the inhibitor mycophenolic acid (MPA), the product XMP with MPA, and XMP with the cofactor NAD(+). In addition, a potassium ion has been located at the dimer interface. A structural model for the kinetic mechanism is proposed.
About this StructureAbout this Structure
1ME9 is a Single protein structure of sequence from Tritrichomonas foetus with and as ligands. Active as IMP dehydrogenase, with EC number 1.1.1.205 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of Tritrichomonasfoetus inosine monophosphate dehydrogenase in complex with substrate, cofactor and analogs: a structural basis for the random-in ordered-out kinetic mechanism., Prosise GL, Luecke H, J Mol Biol. 2003 Feb 14;326(2):517-27. PMID:12559919
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